Abstract

AIMS:

Increasing evidence supports a role for inflammation in promoting atrial fibrillation (AF) and statins have anti-inflammatory effects that may be relevant for the prevention of AF. However, studies of statin therapy and incident AF have yielded mixed results and not focused on individuals with an underlying pro-inflammatory response. We studied whether high-sensitivity C-reactive protein is associated with incident AF and whether treatment with rosuvastatin is associated with a lower incidence of AF compared with placebo.

METHODS AND RESULTS:

We randomized men and women with LDL cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L to receive either rosuvastatin 20 mg daily or placebo. Atrial fibrillation was determined from treatment-blind adverse event reports. Among 17 120 participants without prior history of arrhythmia, each increasing tertile of baseline high-sensitivity C-reactive protein was associated with a 36% increase in the risk of developing AF (95% CI: 1.16-1.60; P-trend < 0.01). Allocation to rosuvastatin when compared with placebo was associated with a 27% reduction in the relative risk of developing AF during the trial period; specifically, AF was reported among 138 participants in the placebo group and 100 in the rosuvastatin group (incidence rate 0.78 vs. 0.56/100 person-years, HR: 0.73, 95% CI: 0.56-0.94, P = 0.01). The exclusion of participants who developed a major cardiovascular event prior to the report of AF yielded similar results.

CONCLUSION:

Within the JUPITER trial cohort of individuals selected for underlying inflammation, increasing levels of high-sensitivity C-reactive protein were associated with an increased risk of incident AF and random allocation to rosuvastatin significantly reduced that risk.

Cumulative incidence of atrial fibrillation according to study group. Shown is the incidence of atrial fibrillation in the placebo and rosuvastatin groups. The P-value was calculated using a likelihood ratio test of the effect of rosuvastatin, using a proportional hazards model.

Effect of rosuvastatin on incident atrial fibrillation according to various baseline characteristics. Shown are hazard ratios (square boxes) for the rosuvastatin group as compared with the placebo group. The size of each square box is inversely proportional to the confidence interval (horizontal lines). Tests of interaction between rosuvastatin and each subgroup variable were non-significant (Peach>0.10). *Hs-CRP, high-sensitivity C-reactive protein.